Benzamide derivatives



iacture.

Patented Aug. 11, 1953 UNITE BENZAMIDE DERIVATIVES Norbert Steiger, Nutley, N. 1., assignor to Hoffmann-La. Roche Inc., Nutley, N. J., a corporation of New Jersey No Drawing. Application May 1, 1951, Serial No. 224,067

This, invention relates to amino-N-[hydroxyethyl(aminoethy1ene)nlbenzamides, wherein n is a small integer, e. g., 1, 2,,etc., and their manu- The new compounds are of interest in the field of cardio-a-ctive agents. They are also useful as intermediates in the preparation of compounds which are of interest in combatting virus infections, such as are disclosed and claimed in my co-pending application, Ser. No. 143,150, filed February 8, 1950, now U. S. Patent No. 2,551,647, of which the instant application is a continuation-in-part.

Th compounds comprising the invention can be prepared by reacting a nitrobenzoyl chloride, which may be substituted or unsubstituted, with an amino(ethyleneamino)ethanol to form the corresponding nitro-N- [hydroxyethyl aminoethylenehilbenzamides; and reducing the latter to form the corresponding amino-N- [hydroxyethyl- (aminoethylene)nlbenzamides; 11. having the same significance already assigned thereto.

The following examples will serve to illustrate the invention.

EXAMPLE 1 p-Amino-N- [,8- (B-hydromyethylamz'no) ethyl] benzamide To 400 cc. of water, 125 grams of fi-(fl-aminm ethylamino) ethanol and 60 grams of sodium carbonate there were added 186 grams of p-nitro benzoylchloride while stirring at 75-90 C. The stirring was continued for 4 hours at 90 C. after which the reaction mixture was diluted with 1000 cc. of water. Upon standing for 16 hours, crystals of p-nitro-N- [fl- (fi-hydroxyethylamino) ethyllbenzamide were formed. The crystals were filtered off and washed with three 100 cc. portions of ice water.

24.0 grams of iron filings, 700 cc. of water and cc. of acetic acid were refluxed for 30 minutes and the prepared p-nitro-N-[fi-(fi-hydroxyethylamino)ethyl]benzamide was added thereto at 90-100 C. together with 150- cc. of water. The mixture was refluxed for 4 hours, and 55 cc. of solution of sodium carbonate and 300 cc. of water added thereto at 90 C. 10 grams of a filter aid were added, the mixture was refluxed and then filtered at 95-100 C. The filter cake was washed with 500 cc. of boiling water, and the filtrat treated with 350 grams of sodium chloride and stirred. The p-amino-N-[p-(B-hydroxyethylamino) ethyl] benzamide crystallized, M. P. 167-169 C.

6 Claims. (01. 260-558) m-Amino-N- [fl- (fi-hydromyethylaminm ethyl] benzamide To 400 cc. of water, 125 grams of Brie-aminoethylamino) ethanol, and grams of sodium carbonate there were added 186 grams of m-"nitrobenzoylchloride with, stirring at '75--90 C. The

stirring was continued for 4 hours at C. after which 1000 cc. of water were added to the reac The mixture was refluxed for 4 hours, and 55 cc;

of 20% sodium carbonate and 300 cc. of water added thereto at -97 C. 10 grams of a filter aid were added, the mixtur was refluxed, and then filtered at 95-100 C. The filter cake was washed with 500 cc. of boiling water and to the filtrate were added 350 grams of sodium chloride. The m-amino-N- 8- (B-hydroxyethylamino) ethyllbenzamide was obtained as a viscous oil.

EXAMPLE 3 o-Amino-N- 8- (B-hydroxyethylamino) ethyl] benzamide To a solution prepared from 70 cc. of fl-(flaminoethylamino) ethanol, 50 grams of sodium carbonate and 250 cc. of water were added at about 40 C. 86 grams of o-nitrobenzoyl chloride. The mixture was stirred for one-half hour at 40 C. and then for an additional hour at 55 to 60 C. The reaction mixture was cooled to 10 C. and the mother liquor decanted from the o-nitro- N [,8 (fi hydroxyethylamino) ethyl] benzamide thus formed. The latter was added to a mixture prepared from 180 grams of iron filings, 15 cc. of acetic acid and 500 cc. of water and the resulting mixture heated at C. for about 6 hours. The reaction mixture was then neutralized by the addition of 25 grams of sodium carbonate, filtered at 95 C. and the filter cake washed with 400 cc. of boiling water. To the filtrate were added 250 grams of sodium chloride. The o-amino N [fi-(fi-hydroxyethylamino)ethyl]- benzamide was obtained as a viscous oil.

3 EXAMPLE 4 3-amino-6-chloro-N- [B- (B-hydromyethylamino) ethyl] benzamide 210' grams of 3-nitro-6-chloro-benz0yl chloride were added at -'75 C. to a solution prepared from 115 grams of fl-(fl-aminoethylam-ino)ethanol, grams of sodium carbonate, and 400 cc. of water. The mixture was stirred for one hour at -90 C. A product was obtained which solidi.- fied on cooling. The 3-nitro-6-chl0rQ-N-[13-( 8- hydroxyethylamino)ethyllbenzamide thus obtained was filtered and washed with water. 30 grams of the compound wereadded to a. mixture of 33 grams of iron filings, 3 cc. of acetic acid, 300 cc. of water and 30 cc. of ethanol and the re.- sulting mixture heated at C. for 4- hours. 8 grams of sodium carbonate in 100 cc. of water were then added to the reaction mixture and the latter filtered at 95 C. To the filtrate were added 90 grams of sodium chloride. The 3-amino-6- chloro -N- [,3- (fi-hydroxyethylamino) ethyl] benzamidewas, obtained, as. an oil.

m-Amino-N-{fi- 8- (fl-hydmxyethylamino) ethylaminolethyl}benzamide 82 grams ofp-bromo ethylamijne hydrobromide, 4L5- grams, of ,3-(Braminoethylamino)ethanol,

and; 80 cc. of water were refluxed at 112 C. for i Upon. cooling thereaction mixture below 20 0.,v

4 amin0]ethyl}benzamide solidified. It was filtered off and added to a mixture of grams of iron filings, 15 cc. of acetic acid and 500 cc. of water and heated at 100 C. for 5 hours. To the reaction mixture were added 30 grams of sodium carbonate, and the mixture was filtered at 95 C. The. filter cake was washed with 260 cc. ofiboiling water. To the filtrate were added grams of sodium chloride. The m-amino-N-{p-[B-(e-hw droxyethylamino) ethylamino] et hyl}benza-mide was obtained as an oil.

I claim:

1. p-Amino-N-EB-(B-hydroxyethylamino) eth yll-benzamide.

2'. m-Amino-N- EB- (fi-hydroxyethylamino) ethyllbenzamide.

3. o-Amino-N-[B-(fi hydroxyethylamino) ethyllbenzamide.

4. 3-amino-6-chloro-N-[p3 (5 hydroxyethylamino) ethyllbenzamide.

5. m-Am-ino-N {fi-Efl 5 hydroxyethylam-i noXethylamino]fethyt}benzamide.

6. A compound having the formula wherein R. represents a member selected from the groupconsisting of H and C1 and n represents a small integer;

NORBER'I STEIGER.

References. Cited in the file of this: patent UNITED STATES PATENTS Number Name Date- 2-,452,313 Morgan Qct. 26', 1.948

FOREIGN PATENTS? Number Country Date 500,476 GreatBrit'ain Feb. 6, 193 

6. A COMPOUND HAVING THE FORMULA 